Biomarkers as predictors of inpatient mortality in fractured neck of femur patients.

INTRODUCTION: Hip fractures are common and it is estimated to cost the National Health Service (NHS) around £2 billion/year. The majority of these patients are elderly and they require careful perioperative management as morbidity and mortality are high. This study aims to look at routinely gathered biomarker data and baseline demographics to evaluate if they may be used to predict inpatient mortality. PATIENTS AND METHODS: The study included 2158 patients from a single Centre over a 5-year period. INCLUSION CRITERIA: age>60, confirmed fractured neck of femur on radiological imaging. EXCLUSION CRITERIA: pathological fractures, patients treated non-operatively, missing data. Univariate followed by multivariate analysis was conducted to identify the independent predictors of inpatient mortality. RESULTS: The variables found to be independent predictors of inpatient mortality were: age > 85, sex (male), albumin < 35, lymphocytes < 1, American Society of Anesthesiologist (ASA) grade > 3. For the final derived multivariate logistic regression model, a receiver operator characteristic (ROC) curve was constructed to assess the ability of the included variables to predict inpatient mortality. The area under the curve was 0.794 which together with sensitivity of 63.2% and a specificity of 79.1% at a cut value of 0.1. CONCLUSION: This paper supports research previously conducted in this field, showing the prognostic value of both biomarker (albumin and lymphocytes), and non-biomarker data (ASA grade, age and gender) in predicting mortality in patients who have sustained a hip fracture.

A Systematic Review of Open and Minimally Invasive Surgery for Treating Recurrent Hallux Valgus.

Background Despite advancements in primary correction of hallux valgus (HV), significant rates of reoperation remain across common techniques, with complications following primary correction up to 50% according to some studies. 1 This study explored different methods of surgery currently used in treating HV recurrence specifically (for which literature on the subject has been limited), evaluating open and adapted minimally invasive surgical (MIS) primary techniques used for revision. Methods In December 2020, literature search for both open and MIS surgical techniques in HV revision was conducted using PubMed, EMBASE, and MEDLINE library databases. Results and Conclusion Of initial 143 publications, 10 were finally included for data synthesis including 273 patients and 301 feet. Out of 301 feet, 80 (26.6%) underwent revision with MIS techniques (involving distal metatarsal osteotomies). Those undergoing grouped MIS revisions had an average improvement of 38.3 in their American Orthopaedic Foot and Ankle Society score, compared to 26.8 in those using open techniques. Revision approaches using grouped MIS techniques showed a postoperative reduction in intermetatarsal angle and HV angle of 5.6 and 18.4 degrees, respectively, compared to 15.5 and 4.4 degrees, respectively, for open techniques. There are, however, limitations in the current literature on MIS techniques in revision HV surgery specifically. MIS techniques grouped did not show worse outcomes or safety concerns compared to open techniques.

Percutaneous Strain Reduction Screws Are a Reproducible Minimally Invasive Method to Treat Long Bone Nonunion.

OBJECTIVES: (1) Evaluate whether initial results from percutaneous treatment of nonunion are reproducible (2) Estimate the relative cost of percutaneous treatment of nonunion versus traditional methods. DESIGN: Retrospective multicentre case series. SETTING: Four Level 1 trauma centers. PATIENTS/PARTICIPANTS: Fifty-one patients (34 men and 17 women) with a median age of 51 years (range 14-81) were treated for nonunion at a median of 10 months (range 4-212) from injury. INTERVENTION: Percutaneous strain reduction screws (PSRS). MAIN OUTCOME MEASURED: Union rates and time to union were compared for patients treated in the developing institution versus independent units as well as with previously published results. RESULTS: Forty-five (88%) patients achieved union at a median time of 5.2 months (range 1.0-24.7) confirming the previously published results for this technique. Comparable results were seen between the developing institution and independent units. No patients experienced adverse events beyond failure to achieve union. PSRS seems to offer savings of between £3177 ($4416) to £11,352 ($15,780) per case compared with traditional methods of nonunion surgery. CONCLUSIONS: PSRS is a safe, efficacious treatment for long bone nonunion and may be more cost-effective than traditional nonunion treatment methods. The promising initial results of this technique have now been replicated outside of the developing institution. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment.

Sensitization to inflammatory pain is a pathological form of neuronal plasticity that is poorly understood and treated. Here we examine the role of the SH3 domain of postsynaptic density 95 (PSD95) by using mice that carry a single amino-acid substitution in the polyproline-binding site. Testing multiple forms of plasticity we found sensitization to inflammation was specifically attenuated. The inflammatory response required recruitment of phosphatidylinositol-3-kinase-C2alpha to the SH3-binding site of PSD95. In wild-type mice, wortmannin or peptide competition attenuated the sensitization. These results show that different types of behavioural plasticity are mediated by specific domains of PSD95 and suggest novel therapeutic avenues for reducing inflammatory pain.

Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin.

Wnt proteins regulate the formation of central synapses by stimulating synaptic assembly, but their role at the vertebrate neuromuscular junction (NMJ) is unclear. Wnt3 is expressed by lateral motoneurons of the spinal cord during the period of motoneuron-muscle innervation. Using gain- and loss-of-function studies in the chick wing, we demonstrate that Wnt signaling is necessary for the formation of acetylcholine receptor (AChR) clusters without affecting muscle growth. Similarly, diaphragms from Dishevelled-1 mutant mice with deficiency in Wnt signaling exhibit defects in cluster distribution. In cultured myotubes, Wnt3 increases the number and size of AChR clusters induced by agrin, a nerve-derived signal critical for NMJ development. Wnt3 does not signal through the canonical Wnt pathway to induce cluster formation. Instead, Wnt3 induces the rapid formation of unstable AChR micro-clusters through activation of Rac1, which aggregate into large clusters only in the presence of agrin. Our data reveal a role for Wnts in post-synaptic assembly at the vertebrate NMJ by enhancing agrin function through Rac1 activation.

Postsynaptic TrkB signaling has distinct roles in spine maintenance in adult visual cortex and hippocampus.

In adult primary visual cortex (V1), dendritic spines are more persistent than during development. Brain-derived neurotrophic factor (BDNF) increases synaptic strength, and its levels rise during cortical development. We therefore asked whether postsynaptic BDNF signaling through its receptor TrkB regulates spine persistence in adult V1. This question has been difficult to address because most methods used to alter TrkB signaling in vivo affect cortical development or cannot distinguish between pre- and postsynaptic mechanisms. We circumvented these problems by employing transgenic mice expressing a dominant negative TrkB-EGFP fusion protein in sparse pyramidal neurons of the adult neocortex and hippocampus, producing a Golgi-staining-like pattern. In adult V1, expression of dominant negative TrkB-EGFP resulted in reduced mushroom spine maintenance and synaptic efficacy, accompanied by an increase in long and thin spines and filopodia. In contrast, mushroom spine maintenance was unaffected in CA1, indicating that TrkB plays fundamentally different roles in structural plasticity in these brain areas.

Analyses of murine postsynaptic density-95 identify novel isoforms and potential translational control elements.

Postsynaptic density-95 (PSD-95) is an evolutionarily conserved synaptic adaptor protein that is known to bind many proteins including the NMDA receptor. This observation has implicated it in many NMDA receptor-dependent processes including spatial learning and synaptic plasticity. We have cloned and characterised the murine PSD-95 gene. In addition, we have identified two previously uncharacterised splice variants of the major murine PSD-95 transcript (PSD-95alpha): PSD-95alpha-2b results from an extension of exon 2 and PSD-95alpha-Delta18 from the temporal exclusion of exon 18. The presence of PSD-95alpha-2b sequences in other PSD-95 family members implicates this peptide stretch as functionally significant. Another potential transcript (PSD-95gamma) was also identified based on examination of EST databases. Immunoprecipitation assays demonstrate that proteins corresponding in size to PSD-95alpha-Delta18 and PSD-95gamma interact with the NMDA receptor, suggesting an important biological role for these isoforms. Finally, we have performed bioinformatics analyses of the PSD-95 mRNA untranslated regions, identifying multiple translational control elements that suggest protein production could be regulated post-transcriptionally. The variety of mRNA isoforms and regulatory elements identified provides for a high degree of diversity in the structure and function of PSD-95 proteins.